Level of severity
94% of akathisia events were mild or moderate in patients treated with VRAYLAR + ADT in the two 6-week MDD studies
Well-established tolerability and safety across 4 indications
Well-established tolerability across weight and metabolics
In 6-week MDD studies, VRAYLAR + ADT-treated patients demonstrated mean weight change of 1.5 lb1
| Mean change at endpoint | Proportion of patients with weight increase ≥7% | |
|---|---|---|
| Placebo + ADT (n=503) | +0.4 lb | 1% |
| VRAYLAR 1.5 mg/day + ADT (n=502) | +1.5 lb | 2% |
| VRAYLAR 3 mg/day + ADT (n=503) | +1.5 lb | 2% |
In the 8-week study, mean weight change was <2 lb in patients treated with VRAYLAR + antidepressant1*
In 6-week MDD studies, VRAYLAR demonstrated metabolic shifts similar to placebo for total cholesterol and fasting triglycerides when taken with an antidepressant1,2
| Total cholesterol | Proportion of patients with metabolic shifts was similar to placebo† |
|---|---|
| Fasting triglycerides | |
| Fasting glucose | 97% of patients did not have a clinically meaningful increase in blood glucose‡ |
| Prolactin (ng/mL)§ | No meaningful increase in mean levels |
Weight change and metabolic shifts were generally consistent in MDD and bipolar I depression studies1
(See bipolar I depression tab above)
*In the 8-week MDD study, 2.5% of people taking VRAYLAR + ADT had a weight increase of ≥7% vs 2% of those taking placebo. The mean weight changes reported in this study were VRAYLAR 1-2 mg/day + ADT (n=273) = +1.98 lb; VRAYLAR 2-4.5 mg/day + ADT (n=273) = +1.98 lb; placebo + ADT (n=266) = 0 lb.1 See additional weight data from 26-week MDD study.
†In the 6- and 8-week MDD studies, proportion of patients with metabolic shifts was similar to placebo. Shift defined as: total cholesterol: normal/borderline (<240 mg/dL) to high (≥240 mg/dL); fasting triglycerides: normal/borderline (<200 mg/dL) to high (≥200 mg/dL).1
‡In the 6-week studies, the proportion of patients with shifts in fasting glucose from normal (<100 mg/dL) to high (≥126 mg/dL): VRAYLAR 1.5 mg/day + ADT=2%; VRAYLAR 3 mg/day + ADT=3.2%; placebo-treated=1.3%. The proportion of patients with shifts in fasting glucose from normal to borderline (≥100 and <126 mg/dL) or from borderline to high was similar in patients treated with VRAYLAR and placebo. In the 8-week study, the shifts in fasting glucose were similar among the VRAYLAR and placebo + ADT groups.1
§In two 6-week MDD studies, mean change from baseline in prolactin levels was 4.1 ng/mL and 3.8 ng/mL in the 1.5 mg/day + ADT group (baseline mean: 9.4 - 9.7) and 2.6 ng/mL and 2.9 ng/mL in the 3 mg/day group + ADT (baseline mean: 11.3 - 11.6) vs 1.2 ng/mL and 0.92 ng/mL in the placebo + ADT group (baseline mean: 9.7 - 10.5). In the 8-week MDD study, the mean change from baseline was 3.8 ng/mL in the 1-2 mg/day + ADT group (baseline mean: 8.8) and 4.1 ng/mL in the 2-4.5 mg/day + ADT group (baseline mean 9.4) vs 0.7 ng/mL in the placebo group (baseline mean: 9.4).2
Well-established safety profile across two 6-week major depressive disorder trials1
Most common adverse reactions in two 6-week MDD studies (≥5% and at least twice that of placebo)1
| Placebo + ADT (n=503) | VRAYLAR 1.5 mg/day + ADT (n=502) | VRAYLAR 3 mg/day + ADT (n=503) | |
|---|---|---|---|
| Insomnia|| | 5% | 9% | 10% |
| Nausea | 3% | 7% | 6% |
| Akathisia¶ | 2% | 7% | 10% |
Most common adverse events in two trials that followed recommended titration.
Rates of somnolence and sedation in VRAYLAR 1.5 mg/day + ADT (5%) and 3 mg/day + ADT (6%) groups were similar to placebo + ADT (4%).2
||Insomnia terms: initial insomnia, insomnia, middle insomnia, poor sleep quality, sleep disorder, terminal insomnia.
¶Akathisia terms: akathisia, psychomotor hyperactivity, feeling jittery, nervousness, tension.
Discontinuation rates
1.4% of VRAYLAR-treated patients discontinued treatment as a result of akathisia compared with 0.4% of placebo-treated patients2
In two 6-week MDD studies, 4% of VRAYLAR-treated patients discontinued treatment compared with 2% of placebo-treated patients when following recommended titration schedule.
There were no adverse reactions leading to discontinuation that occurred at a rate of ≥2% in VRAYLAR patients and at least twice the rate of placebo.
Sexual adverse reactions
Less than 1% of VRAYLAR + ADT-treated patients reported sexual adverse reactions in two 6-week MDD studies2#
| Placebo + ADT (n=503) | VRAYLAR 1.5 mg/day + ADT (n=502) | VRAYLAR 3 mg/day + ADT (n=503) | |
|---|---|---|---|
| Abnormal orgasm | 0% | 0% | 0.2% |
| Decreased libido | 0% | 0.2% | 0% |
| Erectile dysfunction | 0% | 0.2% | 0% |
| Ejaculation failure | 0% | 0.2% | 0% |
| Ejaculation disorder | 0% | 0% | 0% |
#These are self-reported adverse effects. If an adverse effect was not reported during a study, a value of 0 was used.
Well-established tolerability across weight and metabolics
Weight change ≤1.5 lb from baseline to endpoint in pivotal 6- and 8-week studies1*
| Mean change at endpoint | Proportion of patients with weight increase ≥7% | |
|---|---|---|
| Placebo (n=463) | -0.2 lb | 1% |
| VRAYLAR 1.5 mg/day (n=467) | +1.5 lb | 3% |
| VRAYLAR 3 mg/day (n=465) | +0.9 lb | 3% |
Placebo-like impact on lipids and fasting glucose from baseline to endpoint in pivotal studies1,2†
| Total cholesterol | Proportion of patients with metabolic shifts was similar to placebo |
|---|---|
| Fasting triglycerides | |
| Fasting glucose | |
| Prolactin (ng/mL) | No meaningful increase in mean levels |
Weight change and metabolic shifts were generally consistent in MDD and bipolar I depression studies
(See adjunctive MDD tab above)
*Recommended dose range of VRAYLAR is 1.5–3 mg/day for depressive episodes associated with bipolar I.1
†Metabolic shift defined as: fasting glucose: normal (<100 mg/dL) to high (≥126 mg/dL), borderline (≥100 mg/dL and <126 mg/dL) to high; total cholesterol: normal/borderline (<240 mg/dL) to high (≥240 mg/dL); fasting triglycerides: normal/borderline (<200 mg/dL) to high (≥200 mg/dL).1,2
Well-established safety profile across 3 bipolar I depression studies
Most common adverse reactions (≥5% and at least twice that of placebo)1
| Recommended dose range | |||
|---|---|---|---|
| Placebo (n=468) | VRAYLAR 1.5 mg/day (n=470) | VRAYLAR 3 mg/day (n=469) | |
| Nausea | 3% | 7% | 7% |
| Akathisia | 2% | 6% | 10% |
| Restlessness | 3% | 2% | 7% |
| EPS‡ | 2% | 4% | 6% |
Rates of somnolence and sedation in VRAYLAR 1.5 mg/day (7%) and 3 mg/day (6%) groups were similar to placebo (4%)1
>99% of EPS and akathisia events in bipolar I depression studies were mild or moderate4
‡EPS included akinesia, drooling, dyskinesia, dystonia, extrapyramidal disorder, hypokinesia, muscle tightness, musculoskeletal stiffness, myoclonus, oculogyric crisis, salivary hypersecretion, tardive dyskinesia, and tremor.1
Discontinuation rates
Overall, 6% of the patients who received VRAYLAR discontinued treatment due to an adverse reaction, compared with 5% of placebo-treated patients in these trials1
VRAYLAR-treated patients discontinued due to EPS at a rate of 0.4% vs 0% for placebo and discontinued due to akathisia at a rate of 1.5% vs 0% for placebo1§
§EPS excludes akathisia and restlessness.
Monitor patients when initiating or changing the dose of VRAYLAR1
EPS and akathisia were among the most common adverse reactions and were most frequently observed following initiation or up-titration1,4
Sexual adverse reactions
Less than 1% of patients reported sexual adverse reactions across clinical studies2
| Most common reactions included: | |||
|---|---|---|---|
| Placebo (n=468) | VRAYLAR 1.5 mg/day (n=470) | VRAYLAR 3 mg/day (n=469) | |
| Abnormal orgasm | 0% | 0% | 0.4% |
| Decreased libido | 0% | 0.2% | 0% |
| Erectile dysfunction | 0% | 0.6% | 0.9% |
| Delayed ejaculation | 0% | 0% | 0% |
Well-established tolerability across weight and metabolics
Weight change of 1.1 lb from baseline to endpoint in 3-week pivotal studies1*†
| Mean change at endpoint | Proportion of patients with weight increase ≥7% | |
|---|---|---|
| Placebo (n=439) | +0.4 lb | 2% |
| VRAYLAR 3-6 mg/day (n=259) | +1.1 lb | 1% |
Placebo-like impact on lipids and fasting glucose from baseline to endpoint in pivotal studies1,2†‡
| Total cholesterol | Proportion of patients with metabolic shifts was similar to placebo |
|---|---|
| Fasting triglycerides | |
| Fasting glucose | |
| Prolactin (ng/mL) | No meaningful increase in mean levels |
*Recommended dose range of VRAYLAR is 3–6 mg/day for manic and mixed episodes and 1.5–3 mg/day for depressive episodes associated with bipolar I. Doses above 6 mg daily did not appear to have additional benefit over lower doses and a dose-related increase in certain adverse reactions was observed.1
†Data shown from baseline to endpoint by modal daily dose, defined as most frequently administered dose per patient.1
‡Metabolic shift defined as: fasting glucose: normal (<100 mg/dL) to high (≥126 mg/dL), borderline (≥100 mg/dL and <126 mg/dL) to high total cholesterol: normal/borderline (<240 mg/dL) to high (≥240 mg/dL); fasting triglycerides: normal/borderline (<200 mg/dL) to high (≥200 mg/dL).1,2
Well-established safety profile across 3 bipolar I acute manic or mixed studies
Most common adverse reactions (≥5% and at least twice that of placebo)1
| Recommended dose range | |||
|---|---|---|---|
| Placebo (n=442) | VRAYLAR 3-6 mg/day (n=263)§ | VRAYLAR 9-12 mg/day (n=360)§ | |
| EPSII | 12% | 26% | 29% |
| Akathisia | 5% | 20% | 21% |
| Vomiting | 4% | 10% | 8% |
| Dyspepsia | 4% | 7% | 9% |
| Somnolence¶ | 4% | 7% | 8% |
| Restlessness | 2% | 7% | 7% |
>92% of EPS and akathisia events in bipolar I acute manic studies were mild or moderate2
§Data shown from baseline to endpoint (Week 3) by modal daily dose, defined as most frequently administered dose per patient.1
IIEPS included bradykinesia, drooling, dyskinesia, dystonia, extrapyramidal disorder, hypokinesia, muscle rigidity, muscle tightness, musculoskeletal stiffness, oromandibular dystonia, parkinsonism, salivary hypersecretion, and tremor.1
¶Somnolence included hypersomnia, sedation, and somnolence.1
Discontinuation rates1
Overall, 12% of the patients who received VRAYLAR discontinued treatment due to an adverse reaction, compared with 7% of placebo-treated patients in these trials
VRAYLAR-treated patients discontinued due to EPS at a rate of 1% vs 0.2% for placebo and discontinued due to akathisia at a rate of 2% vs 0% for placebo1#
#EPS excludes akathisia and restlessness.
Monitor patients when initiating or changing the dose of VRAYLAR1
EPS and akathisia were among the most common adverse reactions and were most frequently observed following initiation or up‑titration1,6
Weight, metabolics, and prolactin
Weight change ≤2.2 lb from baseline to endpoint in 6-week pivotal studies1*†
| Mean change at endpoint | Proportion of patients with weight increase ≥7% | |
|---|---|---|
| Placebo (n=573) | +0.7 lb | 5% |
| VRAYLAR 1.5-3 mg/day (n=512) | +1.8 lb | 8% |
| VRAYLAR 4.5-6 mg/day (n=570) | +2.2 lb | 8% |
Placebo-like impact on lipids and fasting glucose from baseline to endpoint in pivotal studies1,2†‡
| Total cholesterol | Proportion of patients with metabolic shifts was similar to placebo |
|---|---|
| Fasting triglycerides | |
| Fasting glucose | |
| Prolactin (ng/mL) | No meaningful increase in mean levels |
*Recommended dose range of VRAYLAR is 1.5–6 mg/day for schizophrenia. Doses above 6 mg daily did not appear to have additional benefit over lower doses and a dose-related increase in certain adverse reactions was observed.1
†Data shown from baseline to endpoint (Week 6) by modal daily dose, defined as most frequently administered dose per patient.1,2
‡Metabolic shift defined as: fasting glucose: normal (<100 mg/dL) to high (≥126 mg/dL), borderline (≥100 mg/dL and <126 mg/dL) to high; total cholesterol: normal/borderline (<240 mg/dL) to high (≥240 mg/dL); fasting triglycerides: normal/borderline (<200 mg/dL) to high (≥200 mg/dL).1,2
Long-term maintenance treatment of schizophrenia in adults was assessed in a 92-week study of VRAYLAR1,7
Following a 20-week, open-label phase on a stable dose of VRAYLAR, patients were randomized to VRAYLAR 3-9 mg/day or placebo for a 72-week, double-blind phase.1,7
| 72-week, double-blind phase | ||
|---|---|---|
| Placebo (n=99) | VRAYLAR 3-9 mg/day (n=101) | |
| Weight change (lb)§ | +2.1 | +2.5 |
| Fasting glucose (mg/dL) | +4.1 | +5.4 |
| Fasting triglycerides (mg/dL) | -7.6 | +2.8 |
| Total cholesterol (mg/dL) | -6.5 | -4.1 |
| Prolactin (ng/mL) | -6.4 | -6.7 |
Recommended dose range of VRAYLAR is 1.5-6 mg/day. Doses above 6 mg daily did not appear to have additional benefit over lower doses, and a dose-related increase in certain adverse reactions was observed.
§Proportion of patients with weight gain ≥7% was 10.6% during the open-label phase and 27.0% and 32.3% for VRAYLAR and placebo-treated patients, respectively, during the double-blind phase.7
Observed adverse reactions
Most common adverse reactions from short-term schizophrenia studies (≥5% and at least twice that of placebo)1
| Recommended dose range | |||||
|---|---|---|---|---|---|
| Placebo (n=584) | VRAYLAR 1.5-3 mg/day (n=539)II | VRAYLAR 4.5-6 mg/day (n=575)II | VRAYLAR 9-12 mg/day (n=203)II | ||
| EPS¶ | 8% | 15% | 19% | 20% | |
| Akathisia | 4% | 9% | 13% | 14% | |
>97% of EPS and akathisia events in short-term schizophrenia studies were mild or moderate2
IIData shown from baseline to endpoint (Week 6) by modal daily dose, defined as most frequently administered dose per patient.1,2
¶EPS included bradykinesia, cogwheel rigidity, drooling, dyskinesia, dystonia, extrapyramidal disorder, hypokinesia, masked facies, muscle rigidity, muscle tightness, musculoskeletal stiffness, oculogyric crisis, oromandibular dystonia, parkinsonism, salivary hypersecretion, tardive dyskinesia, torticollis, tremor, and trismus.1
Discontinuation rates1,2
Overall, 9% of the patients who received VRAYLAR discontinued treatment due to an adverse reaction, compared with 12% of placebo-treated patients in these trials
These data include patients who discontinued due to worsening of schizophrenia (ie, untreated illness).
VRAYLAR-treated patients discontinued due to EPS at a rate of 0.3% vs 0.2% for placebo and discontinued due to akathisia at a rate of 0.5% vs 0.2% for placebo1#
#EPS excludes akathisia and restlessness.
Monitor patients when initiating or changing the dose of VRAYLAR1
EPS and akathisia were among the most common adverse reactions and were most frequently observed following initiation or up‑titration1,8
ADT=antidepressant therapy; BP-I=bipolar I disorder; DSM=Diagnostic and Statistical Manual of Mental Disorders; EPS=extrapyramidal symptoms; MDD=major depressive disorder.